The overall objective of this project is to identify the molecular mechanisms by which a characteristic liver gene experssion, serum albumin production, may be altered in the neoplastic state. Albumin is the major product of protein synthesis in the normal adult liver, but in various hepatomas its expression is usually reduced or completely repressed. The rate-limiting components in the post-transcriptional regulation of the albumin gene will be examined in the normal rat liver and compared with the corresponding elements in specific hepatomaa which produce abnormally low amounts of albumin. A complementary DNA (cDNA) to the purified albumin mRNA has been prepared, and it will be used as a specific nucleic acid hybridization probe to determine the quantitative distribution of cytoplasmic albumin mRNA. The identification of a possible nuclear precursor to the mRNA will be attempted, and the nuclear-cytoplasmic transport of albumin RNA sequences will be investigated. Total cDNAs prepared against total poly(A)-containing mRNAs will be employed to examine the sequence complexity relationships between hepatomas and the liver. The general physical and chemical properties of albumin mRNA will be studied. Albumin gene expression will be correlated with that of its embryonic analog, alpha-fetoprotein. The production of alpha-fetoprotein declines dramatically at birth but is re-expressed in most hepatomas. The mRNA for this oncogetal antigen will be isolasted by polysome immunoprecipitation, and a cDNA will be synthesized. The quantitative distribution of alpha-fetoprotein mRNA will be examined in the hepatomas, normal liver, and the developing embryonic liver. The albumin-alpha-fetoprotein relationship is one of the most important model systems currently available for the study of the expression of fetal antigens in cancer. This investigation should lead to a better understanding of the regulatory mechanisms involved in normal gene expression, and mulecular alterations that can occur during this process in cancer.